WO2022033581A1 - Méthode de traitement de dermatite - Google Patents

Méthode de traitement de dermatite Download PDF

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Publication number
WO2022033581A1
WO2022033581A1 PCT/CN2021/112493 CN2021112493W WO2022033581A1 WO 2022033581 A1 WO2022033581 A1 WO 2022033581A1 CN 2021112493 W CN2021112493 W CN 2021112493W WO 2022033581 A1 WO2022033581 A1 WO 2022033581A1
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WIPO (PCT)
Prior art keywords
dermatitis
beta
adrenergic receptor
receptor antagonist
pharmaceutical composition
Prior art date
Application number
PCT/CN2021/112493
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English (en)
Chinese (zh)
Inventor
卢俊玮
钟文宏
柯毓贤
苏中慧
Original Assignee
长庚医疗财团法人林口长庚纪念医院
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Application filed by 长庚医疗财团法人林口长庚纪念医院 filed Critical 长庚医疗财团法人林口长庚纪念医院
Priority to EP21855631.4A priority Critical patent/EP4197532A1/fr
Priority to JP2023501641A priority patent/JP2023536689A/ja
Priority to CN202180056449.8A priority patent/CN116348143A/zh
Priority to US18/021,053 priority patent/US20230293460A1/en
Publication of WO2022033581A1 publication Critical patent/WO2022033581A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics

Definitions

  • the present invention relates to a method for treating dermatitis and the use of a beta-1 adrenergic receptor antagonist for preparing a pharmaceutical composition for treating dermatitis.
  • Dermatitis is a broad term that covers a range of inflammatory skin conditions with different etiologies; common dermatitis symptoms include erythema, scaling, crusting, vesicles , itching, and skin thickening due to chronic inflammation.
  • the main treatments for dermatitis focus on basic skin care with moisturizers and topical treatment with steroids and immunosuppressants; however, long-term use of topical steroids and immunosuppressants for dermatitis can have adverse consequences, such as skin degeneration. Thin and prone to infection, as well as skin burn/irritation and increased risk of skin cancer. In addition to this, some patients with dermatitis do not respond to these treatments (ie, are therapeutically resistant to steroids, immunosuppressants) and continue to suffer extensive skin lesions and intense itching, resulting in physical and mental disability.
  • the present invention provides a method of treating dermatitis.
  • the present invention provides the use of a beta-1 adrenergic receptor antagonist for preparing a pharmaceutical composition for treating dermatitis.
  • the present invention discloses a method of treating dermatitis comprising the step of administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a beta-1 adrenergic receptor antagonist.
  • the present invention discloses the use of a beta-1 adrenergic receptor antagonist for preparing a pharmaceutical composition for treating dermatitis, comprising administering a therapeutically effective amount of beta-1 adrenal gland to a patient in need thereof. The steps of pharmaceutical composition of the hormone receptor antagonist.
  • Figure 1(A) is a photographic image of a patient with eczema who did not respond to high-dose steroids
  • Figure 1(B) is a photographic image of a patient with eczema that was treated with betaxolol on top of the affected area for 2 days;
  • Fig. 2(A) to Fig. 2(C) are patients with eczema induced by topical application of betaxolol to the epidermal growth factor receptor tyrosine kinase inhibitor (osimertinib) on day 0 (Fig. 2(A) )), photo images of efficacy on day 2 (Fig. 2(B)) and day 7 (Fig. 2(C));
  • Fig. 3(A) and Fig. 3(B) are photographs of patients with poorly controlled dermatitis before treatment (Fig. 3(A)) and after 2 days of treatment with betaxolol on the local affected area (Fig. 3(B)) image;
  • Fig. 4(A) and Fig. 4(B) are the patients with poorly controlled dermatitis before treatment (Fig. 4(A)) and after 4 weeks of treatment with betaxolol in the local affected area (Fig. 4(B)). photo image.
  • Fig. 5(A) and Fig. 5(B) are photographs of patients with poorly controlled dermatitis before treatment (Fig. 5(A)) and after 7 days of treatment with betaxolol on the local affected area (Fig. 5(B)) image.
  • the articles “a” and “an” refer to one or more (ie, at least one) grammatical objects of the article.
  • EGFR-TKI epidermal growth A factor receptor tyrosine kinase inhibitor
  • an "effective amount" of an antagonist is one that produces the desired effect compared to an untreated subject; for example, an amount of a beta-1 adrenergic receptor antagonist that reduces symptoms and signs of dermatitis by at least 1% quantity.
  • treatment refers to both therapeutic treatment and prophylactic or preventive measures; persons in need of treatment include those already suffering from dermatitis, as well as those susceptible to dermatitis or those in need of prophylaxis.
  • the present invention relates to the use of a beta-1 adrenergic receptor antagonist for preparing a pharmaceutical composition for treating dermatitis, including administering a drug comprising a therapeutically effective amount of the beta-1 adrenergic receptor antagonist to a patient in need thereof Composition steps.
  • dermatitis is any form of skin inflammation and usually involves itching, dry skin, or a rash on swollen and erythematous skin; other signs and symptoms of dermatitis include blisters, exudates, crusts or The skin flakes off.
  • skin cancer include atopic dermatitis (eczema), targeted therapy-induced dermatitis, steroid-resistant dermatitis, contact dermatitis, seborrheic dermatitis (eg, dandruff), and steatosis Dermatitis.
  • targeted therapy includes drugs that inhibit cancer cell growth by interfering with specific targeted molecules required for cancer development and cancer growth, rather than simply interfering with rapidly dividing cells (eg, conventional chemotherapy), such as kinase inhibitors agents, angiogenesis inhibitors, epidermal growth factor receptor (EGFR) inhibitors (eg, epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs), HER2/neu receptors, or a combination thereof.
  • kinase inhibitors agents angiogenesis inhibitors
  • EGFR epidermal growth factor receptor
  • EGFR-TKIs epidermal growth factor receptor tyrosine kinase inhibitors
  • HER2/neu receptors eg, HER2/neu receptors
  • the dermatitis is substantially free of cracks or erosions.
  • the pharmaceutical composition comprises a beta-1 adrenergic receptor antagonist; in other embodiments, the pharmaceutical composition is substantially free of a beta-2 adrenergic receptor antagonist, a nonselective beta adrenergic receptor antagonist antagonists, antibodies (eg, antibodies against IL4RA or IL-25), or combinations thereof.
  • Beta-1 adrenergic receptor antagonists can be administered with a pharmaceutically acceptable carrier.
  • compositions can be formulated for systemic (eg, oral or intravenous), intradermal, subcutaneous, intramuscular, or topical administration.
  • the pharmaceutical composition can be formulated for topical delivery in one of the following forms: ointment, cream, solution, gel, suspension, spray, or lotion; in other embodiments, the pharmaceutical combination
  • the drug may be formulated for sustained or sustained release.
  • beta-1 adrenergic receptor antagonists include atenolol, betaxolol, bisoprolol, esmolol, acebutolol acebutolol, metoprolol, nebivolol, or a combination thereof.
  • the pharmaceutical composition for preparing the treatment of dermatitis further comprises at least one therapeutic agent effective for dermatitis; such therapeutic agents include but are not limited to steroids (eg prednisolone, Methylprednoslone, betamethasone, dexamethasone, clobetasole, etc.), antihistamines (e.g.
  • the above-described therapeutic agents for the treatment of dermatitis may be used in combination with a pharmaceutical composition comprising a beta-1 adrenergic receptor antagonist.
  • a pharmaceutical composition comprising a beta-1 adrenergic receptor antagonist
  • at least one therapeutic agent for the treatment of dermatitis lesser amounts comprising a beta-1 adrenergic receptor antagonist may be required of pharmaceutical compositions, fewer dosing time points and/or increased time intervals to achieve a therapeutic effect.
  • a pharmaceutical composition comprising a beta-1 adrenergic receptor antagonist to be administered for a particular type of dermatitis; eg, the severity and type of dermatitis , the patient's age, weight, gender, comorbidities, and other drugs administered to the patient.
  • the preferred dose is that which produces a therapeutic effect, such as reduction of symptoms and signs of dermatitis, in a patient in need thereof.
  • one dose is administered daily for a specified number of days (eg, 7 days, 1 month, etc.); in other embodiments, multiple doses may be administered within a day (every 2, 4, 6, or 12 hours, etc.) agent.
  • the present invention also contemplates multiple administrations per day, and administrations over multiple days.
  • a patient with hand eczema had been treated with high-intensity topical steroids (clobetasol ointment twice a day for a week) without any improvement, and presented with erythema and scaling (see Figure 1(A)); thereafter The patient's local affected area was treated with 0.25% (w/w) betaxolol gel twice a day, and after 2 days, the erythema and scales subsided significantly (refer to Figure 1(B)).
  • a patient with systemic dermatitis induced by an epidermal growth factor receptor inhibitor (osimertinib) who received steroids (methylprednisolone (20 mg) twice a day for 21 days) but did not Any improvement (refer to Figure 2(A)); the patient's local affected area was then treated with betaxolol gel twice a day, and the dermatitis was significantly improved after 2 days and 7 days of treatment. (Refer to FIG. 2(B) and FIG. 2(C) ).
  • a middle-aged male patient with hand dermatitis was administered topical steroid ointment (clobetasol ointment (0.025%) twice a day for 21 days), oral antihistamines (desclonide once a day) Ratadine (5 mg) + hydroxyzine (25 mg) twice a day for 21 days) and immunosuppressants (cyclosporine (100 mg) twice a day for 28 days), but the scale and There was no improvement in chronic inflammation (see Figure 4(A)); this patient was subsequently treated with 0.25% (w/w) betaxolol gel applied twice daily to the affected area for 4 weeks , scale and inflammation completely subsided (refer to Figure 4(B)).
  • ⁇ -1 adrenergic receptor antagonists compared with conventional therapeutic agents such as general steroids, antihistamines and immunosuppressants, do have obvious therapeutic ability for dermatitis and have unpredictable effects; although
  • the examples use only betaxolol as a specific beta-1 adrenergic receptor antagonist, but it is only an exemplary beta-1 adrenergic receptor antagonist and is not thereby limited to beta-1 adrenergic receptor antagonists Only betaxolol has the effect of treating dermatitis.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une méthode de traitement de la dermatite et l'utilisation d'un antagoniste de l'adrénorécepteur β-1 dans la préparation d'une composition pharmaceutique pour le traitement de la dermatite. Le procédé comprend l'étape d'application de la composition pharmaceutique comprenant une quantité thérapeutiquement efficace d'un antagoniste de l'adrénorécepteur β-1 à un sujet en ayant besoin.
PCT/CN2021/112493 2020-08-14 2021-08-13 Méthode de traitement de dermatite WO2022033581A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP21855631.4A EP4197532A1 (fr) 2020-08-14 2021-08-13 Méthode de traitement de dermatite
JP2023501641A JP2023536689A (ja) 2020-08-14 2021-08-13 皮膚炎の治療方法
CN202180056449.8A CN116348143A (zh) 2020-08-14 2021-08-13 治疗皮肤炎的方法
US18/021,053 US20230293460A1 (en) 2020-08-14 2021-08-13 Method for treating dermatitis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063065723P 2020-08-14 2020-08-14
US63/065,723 2020-08-14

Publications (1)

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WO2022033581A1 true WO2022033581A1 (fr) 2022-02-17

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US (1) US20230293460A1 (fr)
EP (1) EP4197532A1 (fr)
JP (1) JP2023536689A (fr)
CN (1) CN116348143A (fr)
TW (1) TW202206059A (fr)
WO (1) WO2022033581A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080131517A1 (en) * 2006-09-01 2008-06-05 Abdel Fawzy Time-sustained-release formulations comprising a beta-blocker
US20200206164A1 (en) * 2018-12-28 2020-07-02 Chang Gung Memorial Hospital, Linkou Methods and apparatus for treating a wound
TW202026012A (zh) * 2018-12-28 2020-07-16 長庚醫療財團法人林口長庚紀念醫院 β-1腎上腺素受體拮抗劑用於製備治療傷口之組合物之用途和其設備

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080131517A1 (en) * 2006-09-01 2008-06-05 Abdel Fawzy Time-sustained-release formulations comprising a beta-blocker
US20200206164A1 (en) * 2018-12-28 2020-07-02 Chang Gung Memorial Hospital, Linkou Methods and apparatus for treating a wound
TW202026012A (zh) * 2018-12-28 2020-07-16 長庚醫療財團法人林口長庚紀念醫院 β-1腎上腺素受體拮抗劑用於製備治療傷口之組合物之用途和其設備

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YEN CHI‐FENG, HSU CHAO‐KAI, YANG HSING‐SAN, LEE CHAW‐NING, CHI CHING‐CHI, CHUNG WEN‐HUNG, WANG CHIH‐LIANG, PANG JONG‐HWEI SU, WANG: "Treatment of epidermal growth factor receptor inhibitor‐induced severe paronychia with pyogenic granuloma‐like lesions with topical betaxolol: an open‐label observation study", INTERNATIONAL JOURNAL OF DERMATOLOGY, vol. 59, no. 3, 1 March 2020 (2020-03-01), UK , pages 326 - 332, XP055900388, ISSN: 0011-9059, DOI: 10.1111/ijd.14730 *

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US20230293460A1 (en) 2023-09-21
EP4197532A1 (fr) 2023-06-21
JP2023536689A (ja) 2023-08-29
CN116348143A (zh) 2023-06-27
TW202206059A (zh) 2022-02-16

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